title: Monitoring of technical variation in quantitative high-throughput datasets.
abstract: High-dimensional datasets can be confounded by variation from technical sources, such as batches. Undetected batch effects can have severe consequences for the validity of a study's conclusion(s). We evaluate high-throughput RNAseq and miRNAseq as well as DNA methylation and gene expression microarray datasets, mainly from the Cancer Genome Atlas (TCGA) project, in respect to technical and biological annotations. We observe technical bias in these datasets and discuss corrective interventions. We then suggest a general procedure to control study design, detect technical bias using linear regression of principal components, correct for batch effects, and re-evaluate principal components. This procedure is implemented in the R package swamp, and as graphical user interface software. In conclusion, high-throughput platforms that generate continuous measurements are sensitive to various forms of technical bias. For such data, monitoring of technical variation is an important analysis step.
authors.affiliation: Department of Oncology, Clinical Sciences, Lund University, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Lauss
authors.forename: Ilhami
authors.initials: I
authors.lastname: Visne
authors.forename: Albert
authors.initials: A
authors.lastname: Kriegner
authors.forename: Markus
authors.initials: M
authors.lastname: Ringnér
authors.forename: Göran
authors.initials: G
authors.lastname: Jönsson
authors.forename: Mattias
authors.initials: M
authors.lastname: Höglund
keywords: RNAseq; batch effect; bias; data adjustment; high-throughput analysis; sample annotation